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Thyroglobulin Measurement

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Thyroid Function Testing

Part of the book series: Thyroid Function Testing ((ENDO,volume 28))

Abstract

The thyroglobulin (Tg) gene is encoded by human chromosome 8q24.2–8q24.3 in a 8.5 kb coding sequence covering 48 exons. As illustrated in Fig. 7.1, transcription of the 330 kDa Tg monomeric protein is regulated by a number of transcription factors that include TTF-1, TTF-2, and Pax-8 [1–3]. Posttranslational processing is complex and necessitates multiple molecular chaperones to control the glycosylation, appropriate folding, dimerization, and trafficking of the mature protein to the apical membrane where thyroid peroxidase catalyses the iodination of the hormonogenic sites [1, 3–6]. Comparisons between Tg derived from papillary cancers versus normal thyroid tissue show differences in carbohydrate, iodine content, sulfation, charge, and immunological properties [7–13]. These differences likely result from defective posttranslational processing of tumor-derived Tg leading to the secretion of Tg molecules with an abnormal tertiary structure. Because Tg epitopes are conformational, any alteration in the tertiary structure of the molecule has the potential to disrupt the immunological interaction(s) with the assay reagents [7, 10, 11, 14–16]. The half-life of Tg in serum approximates 3 days and is determined by the terminal sialic acid content of the molecule [17]. Both the sialic acid and iodine content of the Tg derived from papillary tumors tend to be lower than normal, suggesting the possibility for differences in the metabolic clearance of Tg protein secreted by different tumors [8, 17–19]. An accelerated metabolic clearance of tumor-derived Tg could be the reason why serum Tg can be paradoxically low or even undetectable in some patients with a significant tumor burden [11, 12, 20–24].

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Notes

  1. 1.

    Serum Tg values expressed in terms of 1:1 CRM-457 standardization.

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Spencer, C., Petrovic, I. (2010). Thyroglobulin Measurement. In: Brent, G. (eds) Thyroid Function Testing. Thyroid Function Testing, vol 28. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-1485-9_7

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